The proposed studies will systematically examine the cells that control intestinal motility in a panel of mutant mice created by NIH funded mouse mutagenesis projects. This will include anatomic evaluation of the enteric nervous system, the Interstitial Cells of Cajal (intestinal pacemaker cells), and sympathetic innervation to the gut. In addition, the principal investigator will use a recently described imaging technique (diolistic labeling) to examine intestinal smooth muscle, and perform functional motility analysis in mutant mice. The long-term objective of these experiments is to identify novel mutations that affect intestinal motility. These studies are important because defects in intestinal innervation and motility cause significant morbidity and mortality. Medical problems associated with abnormal intestinal motility include Hirschsprung's disease, intestinal pseudo-obstruction, and irritable bowel syndrome.